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12 th Congress of the European Hematology Association Non-Hodgkin’s lymphoma - Biology 0918 JUNCTIONAL ADHESION MOLECULE C DIFFERENTIATES CD27 POSITIVE B LYMPHOCYTES INTO GERMINAL CENTER AND NON-GERMINAL CENTER CELLS AND CONSTITUTES A NEW DIAGNOSTIC MARKER FOR B CELL MALIGNANCIES Th. Matthes, 1 C. Ody, 2 S. Jungblut-Ruault, 1 D. Cossali, 1 M. Barnet, 1 M. Aurrand-Lions, 2 B. Imhof 2 1 University Hospital Geneva, GENEVA, Switzerland; 2 University Medical Cen- ter, GENEVA, Switzerland Differentiation of naïve B cells into plasma cells or memory cells occurs in the germinal centers (GC) of lymph follicles or alternatively via a GC- and T cell independent pathway. It is currently assumed that B cell lymphomas correlate to normal B cell differentiation stages, but the precise correlation of several B cell lymphomas to these two pathways remains controversial. We describe the junctional adhesion molecule C (JAM-C), currently identified at the cell-cell border of endothelial cells, as a new B cell marker with a tightly regulated expression during B cell differentiation. Using RT-PCR as well as western blot analysis on sorted B cells, we first showed that the JAM-C molecule is specifically expressed on B cells. Subsequently, we produced a polyclonal antibody directed against JAM-C and we showed that JAM-C expression is regulated during B cell maturation: immature CD10 + B cell in the bone marrow do not express JAM-C; naïve, mature, peripheral blood B cells express it weakly; CD27 + memory B cells strongly; and bone marrow plasma cells are again JAM-C negative. Of particular interest, JAM-C expression divides CD27 + tonsillar B cells into two subpopulations: JAM- Cneg cells, with a phenotype of germinal center B cells and a high expression of BCL-6, a nuclear proto-oncogene with a pivotal role in GCformation, and JAM-Cpos cells, corresponding to non-germinal B cells, derived partly from the marginal zone. In vitro cultures of the different tonsillar B cell subpopulations (CD27 + Jam-C + , CD27 + JAM-Cneg, CD27negJAM-C + ) confirmed these results, since Ig-secretion measured after 7 days of culture, was minimal in naïve CD27neg cells, CD27 + Jam- C GC cells produced mainly IgG, and non-GC JAM-C + CD27 + B cells mainly IgM. Simultaneous analysis of JAM-C and CD27 expression in peripheral blood lymphocytes (PBLs) from a series of 50 patients with various lymphoproliferative syndromes allowed a clear classification into two types of B cell malignancies: JAM-Cneg lymphomas (CLL, 20/20 patients tested; follicular lymphoma 5/5 patients tested; mantle cell lymphoma, 5/7 patients tested), and JAM-C expressing lymphomas (marginal zone B cell lymphoma (MZBL), 9/12 patients tested; hairy cell leukemia, 6/6 patients tested). Whether the three cases of JAM-Cneg marginal zone lymphomas correspond to bona fide MZBL, to a new subgroup of MZBL, or rather to misdiagnosed atypical CLL cases, will be discussed. In conclusion, we therefore suggest that JAM-C constitutes a new diagnostic marker for the characterisation of lymphoproliferative B cell syndromes, and in particular for the positive diagnosis of lymphomas derived from the marginal zone, e.g. marginal zone B cell lymphoma and hairy cell leukemia. 0919 ROLE OF JUNB IN ALCL LYMPHOMA DEVELOPMENT D. Laimer, 1 P. Vesely, 2 P. Staber, 2 P. Pflegerl, 1 R. Brandes, 1 M. Schlederer, 3 G. Hoefler, 2 L. Kenner1 1 Medical University Vienna, VIENNA, Austria; 2 Medical University of Graz, GRAZ, Austria; 3 LBI for cancer research, VIENNA, Austria Background. Anaplastic large-cell lymphoma (ALCL), a highly malignant form of Non-Hodgkin’s lymphoma, is often associated with the generation of the fusion protein NPM-ALK, involving the genes ALK (Anaplastic Lymphoma Kinase) and NPM (Nucleophosmin). Phenotypically, NPM-ALK positive ALCL is characterized by high expression of CD 30 and of the AP-1 transcription factor family member JunB. Mostly, JunB is viewed as an antioncogene, while the AP-1 family member cJun is a protooncogene. In ALCL, though, JunB seems to act as protooncogene. NPM-ALK is autophosphorylated, functioning as docking station for major signalling pathways (MAPK, JAK/Stat, PI3-K). Aims. In this study we investigate patho-physiological mechanisms underlying tumor formation by the NPM-ALK fusion protein and to improve diagnosis and treatment of ALCL patients. JunB could serve as diagnostic parameter for diagnosis of ALCL lymphomas. JunB or one of its target genes could also be established as a possible therapeutic target. Meth- 344 | haematologica/the hematology journal | 2007; 92(s1) ods. We used both in vivo and in vitro models to define the role of JunB in lymphomagenesis. As in vivo model we crossed transgenic mice harboring the human NPM-ALK fusionprotein expressed under the CD-4 promoter with CD-4 Cre JunBf/f mice, thereby inducing a conditional T-cell JunB knockout (cre/lox system). As in vitro models we used different NPM-ALK positive or negative human ALCL cell lines. Results. AP-1 activity and composition of NPM-ALK positive and negative cell lines was compared by EMSA and supershift analysis. Our results show that AP-1 DNA-Binding activity is NPM-ALK dependent and that the Ap-1 complex in NPM-ALK positive cells mainly consists of JunB. Loss of JunB in T-cells of NPM-ALK transgenic mice does not result in a survival advantage, however, significantly reduced proliferation and apoptosis rates were found in vivo. The mRNA expression of JunB target genes p53 and BCL-X were markedly reduced, the expression of c-Kit and FosB increased. Stat3 protein expression, which was shown to be crucial in ALCL tumor formation, was increased. Summary. NPM-ALK positive ALCL is a highly malignant form of Non-Hodgkin’s lymphoma. We showed in NPM-ALK positive ALCL cell lines that AP-1 complex, consisting largely of JunB is increased. Conditional T-cell specific loss of JunB results in reduced proliferation and apoptosis rates and in a shift in oncogene expression patterns. However, deletion of JunB in the late Tcell development stage does not result in an altered survival rate. 0920 THE ONCOPROTEIN NPM-ALK INDUCES TRANSLATION OF AP-1 FACTORS VIA MTOR SIGNALLING P. Staber, 1 P. Vesely, 1 C. Fuchs, 1 I. Bambach, 1 S. Schauer, 1 H. Bergler, 2 D. Sternberg, 3 G. Hoefler1 1 Medical University Graz, GRAZ, Austria; 2 Karl-Franzens Universität, GRAZ, Austria; 3 Mount Sinai School of Medicine, NEW YORK, USA Background. The nucleophosmin- anaplastic lymphoma kinase fusion protein (NPM-ALK) is the product of the balanced chromosomal rearrangement t(2;5)(p23;q35) and occurs in about half of nodal anaplastic large cell lymphoma (ALCL). ALCLs are highly proliferating tumors and usually express AP-1 transcription factors which are implicated to play a crucial role in oncogenesis. Results. 1) Aberrant NPM-ALK expression induces activation of PI3Kinase/mTOR pathway and AP-1 activity in Ba/F3 cells. 2) mTOR activity is observed in 9/10 NPM-ALK positive compared to 1/15 NPM-ALK negative ALCL patient samples. 3) Inhibition of PI3K by LY294002 or of mTOR by rapamycin in NPM-ALK positive cells decreases proliferation and down-regulates protein levels of the AP-1 factors c-Jun, JunB, and Fra-2. 4) mRNA levels of c-Jun, JunB, and Fra-2 are not affected by PI3K/mTOR inhibition. 5) mRNAs of AP- 1 factors are translated from large polysomes but are shifted to monosomes and ribo-nucleic particles (RNPs) upon PI3K/mTOR inhibition and serum starvation. 6) We found a highly conserved region within the untranslated region of AP-1 mRNA which is involved in translational regulation. Conclusions. Our findings reveal that AP-1 factors are a critical target of mTOR and are translationally deregulated in NPM-ALK positive lymphomas. This is the first study to demonstrate translational control of AP-1 transcription factors in human neoplasia. 0921 ANALYSIS OF MICRORNAS EXPRESSION PATTERN IN CLASSICAL HODGKIN LYMPHOMA A. Navarro, 1 A. Gaya, 2 A. Urbano-Ispizua, 2 A. Pons, 1 A. Martinez, 3 B. Gel, 1 O. Balague, 3 P. Abrisqueta, 2 A. Lopez-Guillermo, 2 R. Artells, 1 E. Montserrat, 2 M. Monzo1 1 University of Barcelona, BARCELONA; 2 Hematology -Hospital Clinic, BARCELONA; 3 Hematopathology Section, Lab of Pathology, BARCELONA, Spain Background. Mature microRNAs (miRNAs) are small non-coding RNA molecules of 21-25 nucleotides that act as negative regulators of translation of mRNA to protein. There is evidence that miRNAs play an important role in carcinogenesis and they can act as oncogene and tumour supressor gene. Is Known that miRNAs expression can define a tumour better than the mRNA expression pattern. Aims. The objective of this study was to analyze the miRNAs expression patterns in lymph nodes from patients with classical Hodgkin lymphoma (cHL) in comparison to reactive lymph nodes. Moreover, we investigated the miRNAs pattern of cHL depending on Epstein-Barr Virus (EBV) presence. Methods. We analyzed 157 mature miRNAs by Real time PCR in ABI PRISM 7500 in 49 lymph nodes from patients diagnosed with cHL (37 Nodular
sclerosis[NS] and 12 Mixed cellularity[MC]) and in 10 reactive lymph nodes (RLN). Patients median age was 32 years (range, 15-80), clinical stage was I-II (n=26); III-IV (n=23) and 25 were EBV+. RNA was obtained from formalin fixed paraffin embedded tissues. Data were analyzed by using BRB Array Tools and TIGR Multiexperiment Viewer. Results. Hierarchical clustering analysis categorized three well defined groups corresponding to NS, MC and RLN. We detect a distinctive miRNAs signature of cHL samples that was compound by a set of 25 miRNAs including miR-21, mir-134 and mir-138, which permits to differentiate between cHL samples and RLN. We applied PAM algorithm to an independent set of 24 samples and using the microRNAs signature of 25 miRNAs the samples were classificated in cHL or RLN correctly in all cases. We also found a specific set of 36 miRNAs differentially expressed between nodular sclerosis and mixed cellularity subtype. With respect to EBV presence, we found that miR-96, 128a, 128b, 129 and 205 were underexpressed in EBV + cases, whereas miR-28, 130b, 132, 140 and 330 were overexpressed. We also found that miR-138 was overexpressed in clinical stages I-II vs. III-IV (p=0.004), and that miR-328 was overexpressed in stages III-IV (p=0.003). We analyze mir-21 and mir-138 by in situ hybridization and found that it were expressed by the tumoral cells. Summary/Conclusions. Classical HL have a specific miRNAs signature that can play a role in its pathogenesis and there are differences between NS or MC subtypes. The presence of EBV affect the miRNAs pattern. 0922 FREQUENT CRYPTIC ALTERATIONS DETECTED BY SNP-CHIPS IN BURKITT LYMPHOMAS V. Havelange, 1 E. Callet-Bauchu, 2 I. Theate, 3 F. Mugneret, 4 L. Michaux, 5 C. Barin, 6 N. Dastugue, 7 E. Lippert, 8 P. Saussoy, 9 D. Penther10 , M. Vikkula11 , H. Poirel12 1 Cliniques Universitaires Saint-Luc, BRUSSELS, Belgium; 2 CHU-Lyon Sud, LYON, France; 3 Laboratoire d’anatomopathologie,St Luc, BRUSSELS, Belgium; 4 Hôpital Bocage, DIJON, France; 5 KUL, LEUVEN, Belgium; 6 CHU Tours, TOURS, France; 7 CHU Purpan, TOULOUSE, France; 8 CHU-Bordeaux, BOR- DEAUX, France; 9 Laboratoire d'hématologie, BRUSSELS, Belgium; 10 Centre Henri Becquerel, ROUEN, France; 11 Human molecular genetic, ICP, BRUSSELS, Belgium; 12 Centre de Génétique Hématologie,St. Luc, BRUSSELS, Belgium Background. Burkitt lymphomas/leukemias (BL), highly aggressive Bcell lymphomas, are characterized by MYC locus rearrangement. Additional chromosomal abnormalities have been described; the most frequent are partial gain of 1q (+1q), 7q (+7q) and partial 13q deletion. We recently demonstrated in a conventional cytogenetic study of childhood mature B-cell lymphomas the independent negative prognostic impact of del(13q) and +7q. Aims. To characterize these prognostic additional chromosomal abnormalities and to look for cryptic genomic alterations in order to reveal candidate genes and/or cellular pathways involved in Burkitt lymphomagenesis. Methods. DNA from 36 BL (20 adults/16 children) was analyzed by 50K Xba SNP arrays (Affymetrix), a genome-wide study of single nucleotide polymorphisms (SNPs). This technique allows the detection of allelic imbalances and losses of heterozygosity (LOH). Results. The most frequent additional chromosomal abnormalities were refined: partial or total gain of 1q and 7q. Recurrent 13q amplification (minimal amplified region of 3.1Mb) was detected in 7 patients followed by a terminal deletion in 4 patients. Different candidate genes are under study. Many cryptic imbalances have been detected by this technique like 2p16.1 amplification containing 2 oncogenes (REL and BCL11a) in 7 patients or 9p21.3 deletion including the tumor suppressor gene (TSG) CDKN2A in 4 patients. 144 acquired partial uniparental disomies (pUPD) (defined as region of at least 50 SNPs) were found by SNP-arrays (4/patient). pUPD are characterized by loss of heterozygosity without chromosomal deletion and probably result from mitotic recombination(s). The physiopathogenic role of pUPD remains unclear. Firstly, it can be polymorphisms. Secondly, random pUPD can reflect genomic instability especially in complex karyotypes. We show a similar incidence of pUPD in BL with or without complex karyotype. Thirdly, non random pUPD may have a pathogenic effect, rendering the cell homozygous for a preexisting mutation leading to activation of an oncogene or inactivation of a TSG. Some regions seem to be non-random in the most probable pUPD of our series: 17p and 17q (n=4), 1p, 9p and 10q (n=3). We are now sequencing candidate genes (CDKN2A, TP53…) in these non random pUPD to unveil mutations of oncogenes or TSG. Conclusions. The SNP arrays allowed us to characterize additional prognostic chromosomal abnormalities in BL and to detect many cryptic non random alterations. Acquired pUPD seem to be localized in non random regions and can be involved in BL pathogenesis in cooperation with MYC deregulation. 12 th Congress of the European Hematology Association Cytogenetics, molecular diagnostics and targeted therapies 0923 HIGH RESPONSE RATE AFTER SEQUENTIAL ADMINISTRATION OF AZACITIDINE, VALPROIC ACID, AND ATRA IN PREVIOUSLY UNTREATED OLDER PATIENTS WITH ACUTE MYELOID LEUKEMIA OR HIGH-RISK MYELODYSPLASTIC SYNDROME E. Raffoux, 1 C. Recher, 2 N. Boissel, 1 R. Oumedaly, 3 I. Lobe, 1 F. Huguet, 2 D. Rea, 1 P. Chaibi, 4 A. De Labarthe, 1 P. Fenaux, 5 L. Degos, 6 C. Gardin, 5 H. Dombret1 1 1Hopital Saint Louis, PARIS, France; 2 CHU Purpan, TOULOUSE, France; 3 CHU Caen, CAEN, France; 4 Hop Ch. Foix, IVRY/SEINE, France; 5 CHU Avicenne, BOBIGNY, France; 6 HAS, ST DENIS, France Background. Intensive chemotherapy is associated with very poor results in older patients with AML or high-risk MDS. Epigenetic modulation combining demethylating agent and HDAC inhibitor seems to be a promising alternative (Garcia-Manero Blood 2006, Soriano ASH 2006). We report here preliminary results of a pilot study using azacitine and valproic acid (VPA) followed by ATRA in this patient population. Patients and Methods. Patients with AML or high-risk MDS aged 60 years or more and considered as unfit for conventional chemotherapy were enrolled. Each treatment cycle comprised azacitidine (75 mg/m 2 /d) and VPA (50 mg/kg/d) for seven days (D1-D7), followed by ATRA (45 mg/m 2 /d) from D8 to D28, every 28 days. A total of 6 cycles was planned. Peripheral blood and marrow evaluation was performed after cycle 1, 3, and 6. AML responses were classified as CR, CRi, PR, NEL (no evidence of leukemia), stable disease with or without haematological improvement (HI), or progressive disease while MDS responses were classified as CR, PR, HI, or progressive disease, according to AML and MDS IWG criteria. Disease progression was assessed only after at least 3 cycles. Results. Between March 2006 and January 2007, 20 patients were treated (median age, 74 years; 12 AML and 8 MDS). AML patients had either severe comorbidities (n=6) or -7/complex karyotype (n=6). All MDS patients had high-risk IPSS Score including 3 patients with -7/3q abn/complex karyotype At the time of analysis, 17 patients were evaluable with a median cycle number of 5. Overall haematological response including HI was 65%. In AML patients, response rate was 66% (8/12) with 6 CR, 1 PR and 1 NEL. In MDS patients, response rate was 60% (3/5) including 1 CR, 1 PR, and 1 HI (HI-E + HI-P). Overall CR + PR rate was thus 53%. Only one death was observed during therapy (1 sepsis after the first cycle). Neurological Grade 3/4 toxicities were observed in 2 patients (transient encephalopathy attributed to VPA by both investigators and independent safety committee). Others side effects were pain at injection site and mild GI events, as described with azacitidine alone. Despite these toxicities, most patients could be treated as out-patients. Conclusions. Combined therapy with azacitidine and VPA followed by ATRA seems to be a relatively safe and very promising approach in older patients with high-risk myeloid disorders. Response rate (53% CR + PR) compares favorably enough with intensive chemotherapy to envision future prospective up-front comparison. 0924 TARGETING ICMT AMELIORATES K-RAS-INDUCED MYELOPROLIFERATIVE DISEASE AND LUNG CANCER M. Bergo, A.M. Wahlstrom, M. Liu, C. Karlsson, B. Swolin, B.A. Cutts Sahlgrenska University Hospital, GOTEBORG, Sweden Background. Hyperactive signaling through the RAS proteins is involved in the pathogenesis of many forms of cancer. The RAS proteins and many other intracellular signaling proteins are methylated at a farnesylated or geranylgeranylated cysteine residue at the carboxyl terminus by isoprenylcysteine carboxyl methyltransferase (ICMT). We previously showed that inactivation of Icmt results in mislocalization of the RAS proteins and blocks oncogenic RAS transformation of mouse fibroblasts suggesting that ICMT may be an attractive therapeutic target. However, nothing is yet known about the impact of inhibiting ICMT on the development of malignancies in vivo. Aim. To test the hypothesis that inactivation of Icmt would inhibit the development or progression of a K-RAS-induced myeloproliferative disease in mice. Methods. We used Cre-loxP techniques to simultaneously activate the expression of endogenous oncogenic K-RAS and inactivate the expression of Icmt in bone marrow cells. In this way, we could determine if the absence of Icmt would have an impact on the development of K-RAS-induced haematologica/the hematology journal | 2007; 92(s1) | 345
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haematologica the hematology journa
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Information for readers, authors an
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EHA Executive Board E. Hellström-L
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Poster session I POSTER SESSION POS
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12 th Congress of the European Hema
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dasatinib. Methods. We studied Ikar
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Expression of the oncogene H-Ras an
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is the gene for the erythropoietin
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safety of a slow-release liposomal
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0029 OUTCOME OF THE TREATMENT OF AD
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drug-induced apoptotic response of
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41% in the PI3K- group (p=0.001). I
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Acute myeloid leukemia - Clinical I
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to 60 years (n=116, or 72%) receive
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0056 PROGNOSTIC SIGNIFICANCE OF FLT
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Anemia and Bone marrow failure 0061
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tified with the current protocol. S
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new cases of lead poisoning due to
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icance, from baseline to week 6 (p
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0086 THROMBELASTOGRAPHIC CHART RELI
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trials. The aim of this retrospecti
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tant function in this disease, nega
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ed to a favorable outcome. Bialleli
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stronger levels of p21 in the cell
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hematological centers in one countr
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ure 1). Conclusions. Results for re
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patients. After a median follow-up
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Cytogenetics and Molecular diagnost
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0135 ROUTINE DETECTION OF CYTOGENET
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(MMolR, defined as a BCR-ABL x 100
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0146 ARSENIC TRIOXIDE INDUCES ACCUM
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tinguish between genotypic B-cell l
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Genomics and proteomics 0158 PLASMA
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0164 EVALUATION OF MULTIPLEX LIGATI
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each patient’s replicate conditio
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0174 RELATION BETWEEN LOW PML-RARα
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0179 ESHAP VS GIN AS SALVAGE AND MO
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Immunology and gene therapy 0184 EA
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Cell viability was not affected by
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month is not relevant to chronic Gv
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Infection and supportive care I 020
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0206 POTENTIAL ROLE OF CMV IN THE O
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3H-thymidine uptake in cell culture
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0217 TUBERCULOSIS AMONG A COHORT OF
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0222 COMPARISON OF IWG 2006 AND IWG
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tem (IPSS) to h-MDS was also invest
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PCH97-19) were studied. Conventiona
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of erythroid colonies was reduced i
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0245 POTENT AND SELECTIVE INHIBITIO
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0250 INACTIVATION OF SUPPRESSOR OF
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Bortezomib 1.3 mg/m 2 days 1,4,8,11
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Response was defined according to E
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G-CSF can be used in neutropenic pa
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ence and functional activity of CD8
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itating tumor development, or engag
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phoma and SNT-13, -15 were establis
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usage (2/20 ie 10%) were observed.
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0294 MYCOSIS FUNGOIDES. IMMUNOHYSTO
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(range, 1-6) and 11 treatment cycle
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0306 RISK-ADAPTED IMMUNOCHEMOTHERAP
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functional activity was confirmed b
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No major toxicity, neither hematolo
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enewal potential of X-RAR-positive
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(50-99) respectively. Serial analys
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cell-interaction, adhesion and acti
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0340 ALTERED FIBRIN CLOT STRUCTURE
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Conclusions. This study demonstrate
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0354 FACTOR V LEIDEN HOMOZYGOUS GEN
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Results. From July 2005 through Mar
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0364 CLINICAL EFFICACY OF OXALIPLAT
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one marrow and peripheral blood ste
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ecently suggested (Boissel et al.,
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0378 SAFETY AND EFFICACY OF THE TER
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Cytogenetics and molecular diagnost
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0385 CYTOPLASMIC MUTATED NUCLEOPHOS
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0390 ELTROMBOPAG RAISES PLATELET CO
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factor for the achievement of CR wa
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The cases of RAS showed two peaks o
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is 85%. Seven out of the 25 relapse
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0409 FRACTIONATED RADIOIMMUNOTHERAP
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0414 COMPARATIVE ANALYSIS OF THE CO
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successfully managed with GM-CSF di
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49% for PCR positive patients (95%
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+8 (1 PR+1 HI) and 14/24 pts with c
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(e.g. bcr-abl leading to CML). CSC
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0438 TERC MUTATIONS ANALYSIS IN PAT
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observed in all mice. Analysis of l
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ex-vivo expansion of HUCB-derived H
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ic kidney disease in univariate or
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One hundred eleven CN AML patients,
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to asses intestinal epithelial dama
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genesis of acute myeloid leukaemia
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polymorphism at nucleotide 4889 of
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expression along with a decreased C
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0487 MUTATIONAL STATUS OF NUCLEOPHO
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previously reported, a single cours
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0497 SINGLE AGENT CLORETAZINE (VNP4
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ly received melphalan-based chemoth
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were similar among the 3 groups. Ho
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Methods. Several read-out systems w
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0518 SERUM AND CELLULAR EXPRESSION
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0523 DNA REPAIR INHIBITION IN RESTO
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held true when BMI-1 expression was
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Ph + cells in the bone marrow). We
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derivative chromosome (4p16, 7p14,
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0545 STABILIZED BONE MARROW IS NOT
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obtained in low (Sokal) risk patien
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median dose intensity being 800 (21
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from pivotal clinical trials. Metho
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Cytogenetics and Molecular diagnost
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to set up and optimize a D-HPLC-bas
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0576 WESTERN BLOT IDENTIFICATION OF
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Basic disease was AML (n=5), ALL (n
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0588 EXTRACORPOREAL PHOTOPHORESIS F
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acquire a cytolytic capacity agains
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informed vignettes describing healt
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using CHOP-21 in the UK, pegfilgras
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0609 SOFT TISSUE COMPLICATIONS IN P
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inding lectin (MBL) gene by polymer
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all infection rate (p=0.12) as well
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Myelodysplastic syndromes II 0623 M
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formation (in total 28 samples). Ti
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sion. In addition, confocal analysi
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Myeloproliferative disorders - Clin
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open-label, multi-centre study enro
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iopsies after 6 and 12 months treat
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Myeloproliferative disorders Chroni
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ash, muscolar cramps, diarrhoea, he
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induced significant apoptosis (mean
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Myeloma and other monoclonal gammop
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the therapy of choice for POEMS is
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er patient does not indicate such t
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Myeloma and other monoclonal gammop
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secutive patients with MM, referred
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whether gene expression values may
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0705 THE SHIFT OF TREATMENT FOR NAS
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0710 CLINICO-PATHOLOGICAL FEATURES,
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patients presented a stage IV disea
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plete remission or recurrent diseas
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known at NHL diagnosis, were includ
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0731 THE IMPACT OF HIV ON NON-HODGK
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patients had died of their underlyi
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scripts and proteins most affected
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modulated after 24 h (37 up- and 59
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0753 A SUSTAINED REMISSION OF IDIOP
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and treatment, has rarely been syst
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uncontrolled massive bleeding affec
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Results. A total of 396 patients we
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C30 questionnaire, and the correspo
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wave length of light of reflected r
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Page 309 and 310: p=0.014 and p=0.003, respectively).
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Page 347 and 348: 2004 to January, 2006. At enrollmen
Page 349 and 350: with a p value of ≥ 0.10. Sets of
Page 351: BRIC 126 and 4N1K) in cells lacking
Page 355 and 356: 0927 MK-0457, A NOVEL MULTIKINASE I
Page 357 and 358: Publication Only 0933 CLINICAL FEAT
Page 359 and 360: HSCT from the available Asian as we
Page 361 and 362: that the incidence of JAK2 mutation
Page 363 and 364: without type 2 diabetes. Methods. T
Page 365 and 366: pts (38.8%) that were isolated (abs
Page 367 and 368: y using the Miltenyi CD34 isolation
Page 369 and 370: 0969 COMPARISON OF CD25 IMMUNOHISTO
Page 371 and 372: cytes was 24 days (range 8-32 days)
Page 373 and 374: a cytogenetic hallmark for M4/M5 su
Page 375 and 376: normal human BM B progenitor cells
Page 377 and 378: 0994 INCIDENCE OF INVASIVE ASPERGIL
Page 379 and 380: 3 of disease relapse.TRM at day+100
Page 381 and 382: survival of five years. This dismal
Page 383 and 384: 1011 FLOW CYTOMETRIC DNA INDEX AND
Page 385 and 386: 1018 THE EFFECT OF THE SUGARBAKER P
Page 387 and 388: 1024 KIR/HLA CLASS I MISMATCHING AN
Page 389 and 390: ment details and thrombotic histori
Page 391 and 392: 1036 INCIDENCE AND SPECTRUM OF INFE
Page 393 and 394: tinely by our stem cell lab prior t
Page 395 and 396: tion to a translocation t(5;14)(q35
Page 397 and 398: ment of CML and induces a high rate
Page 399 and 400: due to reactivation and/or progress
Page 401 and 402: 1063 ABNORMAL METHYLATION STATUS OF
Page 403 and 404:
1069 CLINICAL RELEVANCE OF REGULATO
Page 405 and 406:
1076 SERUM LEVELS OF SOLUBLE HLA CL
Page 407 and 408:
patient is still undergoing intensi
Page 409 and 410:
nificant MVD differences were detec
Page 411 and 412:
dictor of OS (p=0.004). High dose t
Page 413 and 414:
1099 ALTERATIONS IN THE NATURAL KIL
Page 415 and 416:
1105 CYTOGENETIC ABNORMALITIES IN 3
Page 417 and 418:
1110 CONSTITUTIVE ACTIVATION OF STA
Page 419 and 420:
efficacy results with a well-tolera
Page 421 and 422:
unmutated VH genes, and high and lo
Page 423 and 424:
Aims. Aim of this study was to pred
Page 425 and 426:
tested across a wide range of human
Page 427 and 428:
were incidentally diagnosed (52%).
Page 429 and 430:
ß2GP1 may be considered as determi
Page 431 and 432:
characterized in 198 β thalassaemi
Page 433 and 434:
1155 PLATELET AGGREGATION IN CHILDR
Page 435 and 436:
to-pelvic or perineal trauma. No me
Page 437 and 438:
in age. High prevalence of LBM amon
Page 439 and 440:
ecause some of the patients were or
Page 441 and 442:
of the drug is crucial to allow lon
Page 443 and 444:
egarding cost analysis of ASCT in G
Page 445 and 446:
ID Allo-BMT, 1 family one mismatche
Page 447 and 448:
admitted to ICU were discharged des
Page 449 and 450:
events -Postoperative states: 9,19%
Page 451 and 452:
efficacy and decreased atherosclero
Page 453 and 454:
1217 INCIDENCE OF EARLY STAGE IDIOP
Page 455 and 456:
1691GA and 1 homozygous 1691AA. The
Page 457 and 458:
1230 ASSOCIATION OF HEPARANASE GENE
Page 459 and 460:
posed, was: DF = (CD43%+FMC7%+CD79b
Page 461 and 462:
treatment of acute promyelocityc le
Page 463 and 464:
loaded group and 35 (70%) were non-
Page 465 and 466:
mild. Fas and soluble Fas ligand le
Page 467 and 468:
1265 POSACONAZOLE THERAPY IN REFRAC
Page 469 and 470:
ly express the cytoplasmic (inactiv
Page 471 and 472:
findings confirmed the significant
Page 473 and 474:
a less favorable prognosis. Interes
Page 475 and 476:
disease (HD), 4 patients (9%) with
Page 477 and 478:
1295 HEMOPHAGOCYTIC LYMPHOHYSTIOCYT
Page 479 and 480:
phamide 750 mg/m 2 on day 1, vincri
Page 481 and 482:
nomenon is unclear. It has been sug
Page 483 and 484:
oped mild thrombocytopenia (platele
Page 485 and 486:
gle dose of 54mg/m 2 rituximab furt
Page 487 and 488:
patients (pts), 36 male, with acute
Page 489 and 490:
esulting alterations of the endothe
Page 491 and 492:
(range 1-7) and 28,6% of patients h
Page 493 and 494:
three decades. In vivo, Ara-C is tr
Page 495 and 496:
statistical analysis. Results. Seve
Page 497 and 498:
Results. Though there was no recogn
Page 499 and 500:
2% and 19% of patients with or with
Page 501 and 502:
were older than 65 y) which can be
Page 503 and 504:
1376 RESVERATROL INDUCED P53 MEDIAT
Page 505 and 506:
median time of 21 days to reach >0.
Page 507 and 508:
ly. Conclusions. 1. Combined intens
Page 509 and 510:
to the presence of IVS1-6 mutation
Page 511 and 512:
fy predictive factors for these abn
Page 513 and 514:
acute leukemia. However, we cannot
Page 515 and 516:
agents. They involve primarily the
Page 517 and 518:
voriconazole for 2 months followed
Page 519 and 520:
typed using a commercially availabl
Page 521 and 522:
low up of ABL KD mutations’ level
Page 523 and 524:
with development of BC/AP. 2. EVI-1
Page 525 and 526:
1447 THE IMPACT OF DISPARITY IN SHO
Page 527 and 528:
three had visual field defects, two
Page 529 and 530:
acquired mutation most prone to cau
Page 531 and 532:
1466 ROS GENERATION AND APOPTOSIS I
Page 533 and 534:
1473 DIARRHEIC SYNDROME, A CLINICAL
Page 535 and 536:
gene fusion is an independent progn
Page 537 and 538:
1484 EPIDEMIOLOGY AND RESPONSE TO T
Page 539 and 540:
1492 FREQUENCY OF MEDITERRANEAN GLU
Page 541 and 542:
immune globulin was administered at
Page 543 and 544:
maintained on Imatinib 400 mg. Afte
Page 545 and 546:
Hodgkin’s disease is well known,
Page 547 and 548:
gram provided a unique chance to de
Page 549 and 550:
even when ADP-induced plt activatio
Page 551 and 552:
medullary involvement of multiple m
Page 553 and 554:
1540 ADMINISTRATION OF G-CSF AND CH
Page 555 and 556:
1548 QUALITY ANALYSIS OF THE MULTID
Page 557 and 558:
Index of authors A Aapro, M., 0377,
Page 559 and 560:
Bahr, J., 0148 Bai, M., 1551 Baia,
Page 561 and 562:
Bottini, P.V., 1181 Botto, B., 0408
Page 563 and 564:
Chaidos, A., 0456, 0498, 0599, 0686
Page 565 and 566:
De Keersmaecker, K., 0442, 0875 De
Page 567 and 568:
El-Sharkawy, N., 0016 Elwahidi, G.,
Page 569 and 570:
Garcia-Frade, J., 0346, 0680, 1105
Page 571 and 572:
H Haas, N., 0742 Haas, O.A., 0001,
Page 573 and 574:
Jaksic, B., 0127, 0446 Jaksic, O.,
Page 575 and 576:
Körmöczi, G., 0848 Kornblau, S.,
Page 577 and 578:
Lin, L.-I., 0030, 0484 Lin, T., 012
Page 579 and 580:
Massé, A., 0249 Massó, P., 1287,
Page 581 and 582:
Musto, P., 0254, 0401, 0422, 0569,
Page 583 and 584:
Papadavid, E., 1442 Papageorgiou, E
Page 585 and 586:
Probatova, N., 0704 Prochazka, V.,
Page 587 and 588:
Rykavicin, O., 0504 Ryningen, A., 0
Page 589 and 590:
Sirard, C., 0127, 0128 Sirigou, A.,
Page 591 and 592:
Thiebaut, A., 0454 Thieblemont, C.,
Page 593 and 594:
Vincenzi, C., 1060 Viniou, N.-A., 0
Page 595 and 596:
Zouabi, H., 0503, 0999 Zoumbos, N.C
Page 597 and 598:
Page 599 and 600:
Page 601 and 602:
Page 603:
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